WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406290
CAS#: 571203-78-6
Description: Erastin is an antitumor agent selective for tumor cells bearing oncogenic RAS (i.e. HRAS, KRAS). Erastin produces non-apoptotic tumor cell death by altering mitochondrial voltage-dependent anion channel (VDAC) gating allowing cations to enter mitochondria and leading to release of oxidative species causing oxidative cell death. Erastin blocks and reverses mitochondrial depolarization after microtubule destabilizers in intact cells and antagonized tubulin-induced VDAC blockage in planar bilayers. Reversal of tubulin-VDAC interaction by erastin antagonizes Warburg metabolism and restores oxidative mitochondrial metabolism.
Hodoodo Cat#: H406290
Name: Erastin
CAS#: 571203-78-6
Chemical Formula: C30H31ClN4O4
Exact Mass: 546.20
Molecular Weight: 547.045
Elemental Analysis: C, 65.87; H, 5.71; Cl, 6.48; N, 10.24; O, 11.70
Synonym: Erastin
IUPAC/Chemical Name: 2-(1-(4-(2-(4-chlorophenoxy)acetyl)piperazin-1-yl)ethyl)-3-(2-ethoxyphenyl)quinazolin-4(3H)-one
InChi Key: BKQFRNYHFIQEKN-UHFFFAOYSA-N
InChi Code: InChI=1S/C30H31ClN4O4/c1-3-38-27-11-7-6-10-26(27)35-29(32-25-9-5-4-8-24(25)30(35)37)21(2)33-16-18-34(19-17-33)28(36)20-39-23-14-12-22(31)13-15-23/h4-15,21H,3,16-20H2,1-2H3
SMILES Code: O=C1N(C2=CC=CC=C2OCC)C(C(N3CCN(C(COC4=CC=C(Cl)C=C4)=O)CC3)C)=NC5=C1C=CC=C5
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Erastin is a ferroptosis inducer which binds and inhibits voltage-dependent anion channels (VDAC2/VDAC3). |
| In vitro activity: | The radiosensitizing effects of erastin on HeLa and NCI-H1975 cells were evaluated (Fig 3). The treatment with a combination of erastin and X-ray irradiation significantly decreased the survival of both the cancer cell lines (two-way ANOVA, p < 0.0001 for treatment with erastin and p < 0.0001 for X-ray irradiation in both the HeLa and NCI-H1975 cells) (Fig 3). The 10% lethal doses (D10) for the X-irradiated HeLa cells with and without treatment with erastin were 10.24 and 8.10 Gy, respectively (sensitizer enhancement ratio [SER] = 1.27). Similarly, the D10 values for the X-irradiated NCI-H1975 cells with and without treatment with erastin were 6.11 and 4.42 Gy, respectively (SER = 1.38). Reference: PLoS One. 2019 Dec 4;14(12):e0225931. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892486/ |
| In vivo activity: | For in vivo studies, NCI-H1975 cells were transplanted in the left shoulder of nude mice, and then radiosensitizing effect of erastin and glutathione concentration in the cancer were evaluated. The group administered with both erastin treatment and radiotherapy showed significant tumor growth suppression, while the group administered with erastin or radiotherapy alone showed no tumor growth suppression (Fig 4A). The values of tumor volume (mean ± S.E) at 14 days after irradiation were 1753.84 ± 288.67 mm3 for Control, 1738.52 ± 309.95 mm3 for X-ray alone, 1719.07 ± 203.13 mm3 for erastin alone, and 1079.89 ± 227.84 mm3 for erastin + X-ray. Furthermore, a glutathione quantification assay revealed that the intratumoral glutathione concentrations in erastin-treated tumors were significantly lower than those in nontreated tumors (Fig 4B). Reference: PLoS One. 2019 Dec 4;14(12):e0225931. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892486/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 10.0 | 18.28 | |
| DMSO | 14.9 | 27.16 | |
| DMSO:PBS (pH 7.2) (1:2) | 0.3 | 0.46 | |
| Water | 0.5 | 0.91 |
The following data is based on the product molecular weight 547.04 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Shibata Y, Yasui H, Higashikawa K, Miyamoto N, Kuge Y. Erastin, a ferroptosis-inducing agent, sensitized cancer cells to X-ray irradiation via glutathione starvation in vitro and in vivo. PLoS One. 2019 Dec 4;14(12):e0225931. doi: 10.1371/journal.pone.0225931. PMID: 31800616; PMCID: PMC6892486. 2. Oh BM, Lee SJ, Park GL, Hwang YS, Lim J, Park ES, Lee KH, Kim BY, Kwon YT, Cho HJ, Lee HG. Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway. J Clin Med. 2019 Dec 14;8(12):2210. doi: 10.3390/jcm8122210. PMID: 31847346; PMCID: PMC6947339. |
| In vitro protocol: | 1. Shibata Y, Yasui H, Higashikawa K, Miyamoto N, Kuge Y. Erastin, a ferroptosis-inducing agent, sensitized cancer cells to X-ray irradiation via glutathione starvation in vitro and in vivo. PLoS One. 2019 Dec 4;14(12):e0225931. doi: 10.1371/journal.pone.0225931. PMID: 31800616; PMCID: PMC6892486. 2. Oh BM, Lee SJ, Park GL, Hwang YS, Lim J, Park ES, Lee KH, Kim BY, Kwon YT, Cho HJ, Lee HG. Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway. J Clin Med. 2019 Dec 14;8(12):2210. doi: 10.3390/jcm8122210. PMID: 31847346; PMCID: PMC6947339. |
| In vivo protocol: | 1. Shibata Y, Yasui H, Higashikawa K, Miyamoto N, Kuge Y. Erastin, a ferroptosis-inducing agent, sensitized cancer cells to X-ray irradiation via glutathione starvation in vitro and in vivo. PLoS One. 2019 Dec 4;14(12):e0225931. doi: 10.1371/journal.pone.0225931. PMID: 31800616; PMCID: PMC6892486. 2. Oh BM, Lee SJ, Park GL, Hwang YS, Lim J, Park ES, Lee KH, Kim BY, Kwon YT, Cho HJ, Lee HG. Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway. J Clin Med. 2019 Dec 14;8(12):2210. doi: 10.3390/jcm8122210. PMID: 31847346; PMCID: PMC6947339. |
1: Maldonado EN, Sheldon KL, DeHart DN, Patnaik J, Manevich Y, Townsend DM, Bezrukov SM, Rostovtseva TK, Lemasters JJ. Voltage-dependent anion channels modulate mitochondrial metabolism in cancer cells: regulation by free tubulin and erastin. J Biol Chem. 2013 Apr 26;288(17):11920-9. doi: 10.1074/jbc.M112.433847. Epub 2013 Mar 7. PubMed PMID: 23471966; PubMed Central PMCID: PMC3636879.
2: Yamaguchi H, Hsu JL, Chen CT, Wang YN, Hsu MC, Chang SS, Du Y, Ko HW, Herbst R, Hung MC. Caspase-independent cell death is involved in the negative effect of EGF receptor inhibitors on cisplatin in non-small cell lung cancer cells. Clin Cancer Res. 2013 Feb 15;19(4):845-54. doi: 10.1158/1078-0432.CCR-12-2621. Epub 2013 Jan 23. PubMed PMID: 23344263; PubMed Central PMCID: PMC3703145.
3: Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012 May 25;149(5):1060-72. doi: 10.1016/j.cell.2012.03.042. PubMed PMID: 22632970; PubMed Central PMCID: PMC3367386.
4: Bauer AJ, Gieschler S, Lemberg KM, McDermott AE, Stockwell BR. Functional model of metabolite gating by human voltage-dependent anion channel 2. Biochemistry. 2011 May 3;50(17):3408-10. doi: 10.1021/bi2003247. Epub 2011 Apr 6. PubMed PMID: 21425834; PubMed Central PMCID: PMC3082971.
5: Simamura E, Shimada H, Hatta T, Hirai K. Mitochondrial voltage-dependent anion channels (VDACs) as novel pharmacological targets for anti-cancer agents. J Bioenerg Biomembr. 2008 Jun;40(3):213-7. doi: 10.1007/s10863-008-9158-6. Review. PubMed PMID: 18704666.
6: Yang WS, Stockwell BR. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol. 2008 Mar;15(3):234-45. doi: 10.1016/j.chembiol.2008.02.010. PubMed PMID: 18355723; PubMed Central PMCID: PMC2683762.
7: Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I, Peltier JM, Boniface JJ, Smith R, Lessnick SL, Sahasrabudhe S, Stockwell BR. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature. 2007 Jun 14;447(7146):864-8. PubMed PMID: 17568748; PubMed Central PMCID: PMC3047570.
8: Gangadhar NM, Stockwell BR. Chemical genetic approaches to probing cell death. Curr Opin Chem Biol. 2007 Feb;11(1):83-7. Epub 2006 Dec 14. Review. PubMed PMID: 17174591; PubMed Central PMCID: PMC3057070.
9: Dolma S, Lessnick SL, Hahn WC, Stockwell BR. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell. 2003 Mar;3(3):285-96. PubMed PMID: 12676586.
